UMIN-CTR Clinical Trial

Public title

Phase II study of gemcitabine plus oxaliplatin combination therapy (GEMOX therapy) for the advanced pancreatic adenocarcinoma with a family history of pancreatic/breast/ovarian/prostate cancer or with a personal history of breast/ovarian/prostate cancer.

Acronym

FABRIC study

Scientific Title

Phase II study of gemcitabine plus oxaliplatin combination therapy (GEMOX therapy) for the advanced pancreatic adenocarcinoma with a family history of pancreatic/breast/ovarian/prostate cancer or with a personal history of breast/ovarian/prostate cancer.

Scientific Title:Acronym

FABRIC study

Region

Japan

Condition

Metastatic pancreatic cancer patients with a family history of pancreatic/breast/ovarian/prostate cancer or with a personal history of breast/ovarian/prostate cancer.

Classification by specialty

Hepato-biliary-pancreatic medicine

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To evaluate the efficacy of gemcitabine and oxaliplatin combination therapy in metastatic pancreatic cancer patients with with a family history of pancreatic/breast/ovarian/prostate cancer or with a personal history of breast/ovarian/prostate cancer.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

1-year survival rate

Key secondary outcomes

Overall survival, Progression-free survival, response rate, adverse events

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Gemcitabine plus oxaliplatin combination therapy:
Gemcitabine (1,000mg/m2, div, over 100 minutes, day1), Oxaliplatin (100mg/m2, div, over 120 minutes, day1), every 2 weeks

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

80

years-old

>

Gender

Male and Female

Key inclusion criteria

1) Diagnosed as pancreatic cancer with histologically or cytologically proven adenocarcinoma
2) Metastatic pancreatic cancer
3) Aged 20 to 79 years old
4) ECOG Performance Status of 0, 1 or 2
5) Patient who meet at least one of the following:
a) Patient who has one or more first-degree relatives with pancreatic, breast, ovarian and/or prostate cancer (Gleason score >=7).
b) Patient who has two or more close blood relatives (first- , second-, and third-degree relatives) with pancreatic, breast, ovarian and/or prostate cancer (Gleason score >=7) on same side of family.
c) Personal history of breast, ovarian and/or prostate cancer (Gleason score >=7)
6) Patients who are determined that FOLFIRINOX therapy and gemcitabine plus nab-paclitaxel therapy are not suitable by the attending physician. However on receiving a explanation of FOLFIRINOX therapy and GEM + nab-paclitaxel therapy, patients who wish to participate in the current study could be enrolled.
7) Previously untreated with systemic chemotherapy for pancreatic cancer other than neoadjuvant or adjuvant chemotherapy ended more than 6 months before
8) Meets the following criteria within 7days before enrollment
a) White blood cell count =< 12,000/mm3
b) Absolute neutrophil count >= 1,000/mm3,
c) Hemoglobin >= 9.0 g/dL
d) Platelet count >= 100,000/mm3
e) Total bilirubin =< 2.0 mg/dl; however, =< 3.0mg/dl in a subject who is treated with biliary drainage
f) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 100 IU/l; however, =< 150 IU/l in a subject who has liver metastases
g) Serum creatinine =< 1.2 mg/dl or caclculated creatinine clearance (by the Cockcroft-Gault formula) >= 60 ml/minutes.
9) Written informed consent

Key exclusion criteria

1) Synchronous or metachronous (within 3 years) malignancies except carcinoma in situ or intramucosal tumor curatively treated with local therapy
2) Known metastasis to the central nervus system
3) Presence of uncontrollable moderate or severe ascites and/or pleural effusion
4) Grade 2 or more of peripheral sensory neuropathy or peripheral motor neuropathy
5) Oral intake is impossible
6) Major surgery within 4 weeks
7) Blood transfusion or G-CSF within 2 weeks
8) Patients requiring systemic steroids medication
9) Unstable angina pectoris within 3 weeks, or with a history of myocardial infarction within 6 months
10) Interstitial pneumonia, pulmonary fibrosis
11) Severe complications such as heart failure, renal failure, liver failure, peptic ulcer with active bleeding, intestinal paralysis, uncontrolled diabetes mellitus, etc
12) Active infection requiring systemic therapy
13) Pregnant or lactating women or women of childbearing potential, Male expecting partner's pregnancy
14) Psychosis or severe mental disorder
15) History of sever allergic reaction to gemcitabine or oxaliplatin
16) Impossible to use both iodine and gadolinium due to being allergic to contrast agent
17) Inadequate physical condition, as diagnosed by attending physician

Target sample size

43

Name of lead principal investigator

1st name	Chigusa
Middle name
Last name	Morizane

Organization

National Cancer Center Hospital

Division name

Department of Hepatobiliary and Pancreatic Oncology

Zip code

104-0045

Address

5-1-1. Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan

TEL

(+81)03-3542-2511

Email

cmorizan@ncc.go.jp

Name of contact person

1st name	Hideaki
Middle name
Last name	Takahashi

Organization

National Cancer Center Hospital East

Division name

Department of Hepatobiliary and Pancreatic Oncology

Zip code

277-8577

Address

6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

TEL

(+81)04-7133-1111

Homepage URL

Email

hidetaka@east.ncc.go.jp

Institute

National Cancer Center Hospital

Institute

Department

Personal name

Organization

National Cancer Center

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

National Cancer Center Hospital Certified Review Board

Address

5-1-1, Tukiji, Chuo-ku, Tokyo

Tel

03-3542-2511

Email

NCC_IRBoffice@ml.res.ncc.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

札幌厚生病院(北海道）
北海道大学病院（北海道）
手稲渓仁会病院（北海道）
札幌医科大学附属病院（北海道）
栃木県立がんセンター（栃木県）
自治医科大学（栃木県）
高崎総合医療センター（群馬県）
埼玉県立がんセンター（埼玉県）
東京女子医科大学八千代医療センター（千葉県）
国立がん研究センター東病院（千葉県）
杏林大学医学部付属病院（東京都）
国際医療福祉大学三田病院（東京都）
慶應義塾大学病院（東京都）
国立国際医療研究センター（東京都）
東京女子医科大学病院（東京都）
がん研究会有明病院（東京都）
帝京大学医学部附属病院（東京都）
東海大学医学部付属病院（東京都）
国立がん研究センター中央病院（東京都）
神奈川県立がんセンター（神奈川県）
聖マリアンナ医科大学病院（神奈川県）
佐久総合病院 佐久医療センター（長野県）
新潟県立がんセンター新潟病院（新潟県）
石川県立中央病院（石川県）
金沢大学附属病院（石川県）　
愛知県がんセンター中央病院（愛知県）
国立病院機構　大阪医療センター（大阪府）
大阪府立急性期・総合医療センター（大阪府）
京都府立医科大学附属病院（京都府）
京都大学医学部附属病院（京都府）
神戸大学医学部附属病院（兵庫県）
兵庫県立がんセンター（兵庫県）
神戸市立医療センター 中央市民病院（兵庫県）
鳥取大学医学部附属病院（鳥取県）
香川大学医学部附属病院（香川県）
四国がんセンター（愛媛県）
九州がんセンター（福岡県）
長崎大学病院（長崎県）
佐賀大学医学部附属病院（佐賀県）
佐賀県医療センター好生館（佐賀県）
宮崎大学医学部附属病院（宮崎県）
鹿児島大学病院（鹿児島県）
中頭病院（沖縄県）

Date of disclosure of the study information

2015

Year

06

Month

17

Day

URL releasing protocol

not publised

Publication of results

Published

URL related to results and publications

https://pubmed.ncbi.nlm.nih.gov/32535711/

Number of participants that the trial has enrolled

45

Results

Among the first 43 enrolled patients, the 1-year survival rate was 27.9% (90% CI 17.0-41.3). This trial did not meet its primary endpoint because the lower limit of the 90% CI was lower than the prespecified threshold of 30%.

Results date posted

2020

Year

06

Month

16

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

There were 17 men (38%), and the median patient age was 68 years (range 28-79 years). There were two patients (4%) with a PS of two. Peritoneal metastasis and ascites were observed in 44 and 42% of patients, respectively, and 93% of patients had a family history of pancreatic, breast, ovarian, or prostate cancer in FDRs. Forty-three, 25, two, and six patients had relatives with pancreatic, breast, ovarian, and prostate cancer, respectively; these categories are not mutually exclusive. Most of the patients (84%) desired to participate in this trial despite being suitable for FOLFIRINOX or GEM plus nab-PTX.

Participant flow

Between July 2015 and March 2017, 45 patients were enrolled. As pre-planned, 43 patients were included in the primary endpoint evaluation. All 45 patients were included in efficacy evaluations other than for the primary endpoint. One patient who did not receive any study treat-ment because of tumor progression was excluded, and the remaining 44 patients were included in the safety evaluation. The data cutoff date was October 2018.

Adverse events

The most common grade three or four AEs were hematological toxicities. Neutropenia, leukopenia, and thrombocytopenia occurred in 36%, 27%, and 20% of patients, respectively. There was one patient (2%) who developed febrile neutropenia. The most common nonhematological grade three or four AEs were anorexia (14%), fatigue (11%), and elevated ALT (20%). There was no treatment-related death.

Outcome measures

The primary endpoint was 1-year survival defined as the proportion of patients whose OS exceeded 365.25 days, considering leap years.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2015

Year

05

Month

12

Day

Date of IRB

2015

Year

02

Month

27

Day

Anticipated trial start date

2015

Year

06

Month

19

Day

Last follow-up date

2019

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2015

Year

06

Month

13

Day

Last modified on

2020

Year

06

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020460